Comparison of gene expression patterns and migration capability at quiescent and proliferating vascular smooth muscle cells stimulated by cytokines.

The changes of the gene expression patterns and the migration capability of vascular smooth muscle cells (VSMC) at the quiescent and proliferating states were investigated after VSMC was stimulated by cytokines. VSMC migration was measured using a model of wounding injury of confluent cultured cells and a Boyden chamber assay. The migration distance of the quiescent VSMC induced by cytokines bFGF, IL-1beta and TNF-alpha was 5.8, 4.7, and 4.2 times as long as that of the control group, respectively. However, the migration distance of the proliferating VSMC was only one-fourth of the quiescent cells under the same effects. The results of Boyden chamber assay indicated that VSMC was capable of degrading collagen and traversed the pores of membrane barriers in response to bFGF as a chemoattractant, and VSMC number across the membrane was markedly increased as concentration gradient of bFGF ascended. Northern blot and nuclear run-off assay showed that bFGF not only stimulated the expression of migration-related matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) but also enhanced the transcription of proliferation-related osteopontin (OPN) and c-jun genes in the quiescent VSMC. bFGF could moderately increase the expression of OPN and c-jun, but had no significant effect on the expression of MMP-2 and TIMP-2 in the proliferating cells under the same conditions. These findings suggest that VSMC migration capability and the expression activity of migration- and proliferation-related genes were significantly distinct for the quiescent and proliferating VSMC. The cellular migration capability and the expression activity of migration-related genes in the quiescent VSMC were much higher than those in the proliferating cells in response to cytokines.